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Mechanisms of disease: genetic insights into the etiology of type 2 diabetes and obesity.

Abstract

Until recently, progress in identification of the genetic variants influencing predisposition to common forms of diabetes and obesity has been slow, a sharp contrast to the large number of genes implicated in rare monogenic forms of both conditions. Recent advances have transformed the situation, however, enabling researchers to undertake well-powered scans able to detect association signals across the entire genome. For type 2 diabetes, the six high-density genome-wide association studies so far performed have extended the number of loci harboring common variants implicated in diabetes susceptibility into double figures. One of these loci, mapping to the fat mass and obesity associated gene (FTO), influences diabetes risk through a primary effect on fat mass, making this the first common variant known to influence weight and individual risk of obesity. These findings offer two main avenues for clinical translation. First, the identification of new pathways involved in disease predisposition-for example, those influencing zinc transport and pancreatic islet regeneration in the case of type 2 diabetes-offers opportunities for development of novel therapeutic and preventative approaches. Second, with continuing efforts to identify additional genetic variants, it may become possible to use patterns of predisposition to tailor individual management of these conditions.

Authors+Show Affiliations

Wellcome Trust Centre for Human Genetics at the University of Oxford, Oxford, UK.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

18212765

Citation

Lindgren, Cecilia M., and Mark I. McCarthy. "Mechanisms of Disease: Genetic Insights Into the Etiology of Type 2 Diabetes and Obesity." Nature Clinical Practice. Endocrinology & Metabolism, vol. 4, no. 3, 2008, pp. 156-63.
Lindgren CM, McCarthy MI. Mechanisms of disease: genetic insights into the etiology of type 2 diabetes and obesity. Nat Clin Pract Endocrinol Metab. 2008;4(3):156-63.
Lindgren, C. M., & McCarthy, M. I. (2008). Mechanisms of disease: genetic insights into the etiology of type 2 diabetes and obesity. Nature Clinical Practice. Endocrinology & Metabolism, 4(3), pp. 156-63. doi:10.1038/ncpendmet0723.
Lindgren CM, McCarthy MI. Mechanisms of Disease: Genetic Insights Into the Etiology of Type 2 Diabetes and Obesity. Nat Clin Pract Endocrinol Metab. 2008;4(3):156-63. PubMed PMID: 18212765.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mechanisms of disease: genetic insights into the etiology of type 2 diabetes and obesity. AU - Lindgren,Cecilia M, AU - McCarthy,Mark I, Y1 - 2008/01/15/ PY - 2007/09/05/received PY - 2007/11/16/accepted PY - 2008/1/24/pubmed PY - 2008/6/28/medline PY - 2008/1/24/entrez SP - 156 EP - 63 JF - Nature clinical practice. Endocrinology & metabolism JO - Nat Clin Pract Endocrinol Metab VL - 4 IS - 3 N2 - Until recently, progress in identification of the genetic variants influencing predisposition to common forms of diabetes and obesity has been slow, a sharp contrast to the large number of genes implicated in rare monogenic forms of both conditions. Recent advances have transformed the situation, however, enabling researchers to undertake well-powered scans able to detect association signals across the entire genome. For type 2 diabetes, the six high-density genome-wide association studies so far performed have extended the number of loci harboring common variants implicated in diabetes susceptibility into double figures. One of these loci, mapping to the fat mass and obesity associated gene (FTO), influences diabetes risk through a primary effect on fat mass, making this the first common variant known to influence weight and individual risk of obesity. These findings offer two main avenues for clinical translation. First, the identification of new pathways involved in disease predisposition-for example, those influencing zinc transport and pancreatic islet regeneration in the case of type 2 diabetes-offers opportunities for development of novel therapeutic and preventative approaches. Second, with continuing efforts to identify additional genetic variants, it may become possible to use patterns of predisposition to tailor individual management of these conditions. SN - 1745-8374 UR - https://www.unboundmedicine.com/medline/citation/18212765/Mechanisms_of_disease:_genetic_insights_into_the_etiology_of_type_2_diabetes_and_obesity_ L2 - http://dx.doi.org/10.1038/ncpendmet0723 DB - PRIME DP - Unbound Medicine ER -